摘要
人们对于金鸡纳碱的研究已经几十年了,由于金鸡纳碱具有优良的刚性骨架和良好的催化活性位点,它常被用于不对称催化反应的诱导配体,而且表现出优异的催化性能。金鸡纳碱C9上羟基表现出的活性引人关注,1995年德国的Henri Brunner等人改进了前人的工作,在金鸡纳碱的C9位点上引入氨基结构,开启了9-氨基金鸡纳碱衍生物研究的先河。
本文以廉价易得的辛可尼定(CD)为起始原料,将9-羟基用氨基进行取代,同时发生伞转效应合成9-氨基金鸡纳碱衍生物1,再将其与丙烯腈进行不同比例的聚合,使之成为聚丙烯睛类高分子聚合物锚定金鸡纳碱衍生伯胺催化剂,实现了将金鸡纳碱衍生物负载到聚丙烯腈类高分子上
本文合成的聚丙烯腈类高分子负载金鸡纳碱伯胺催化剂2a-d,通过核磁共振(NMR)、傅立叶变换红外光谱(FT-IR)、热重分析(TG)、X-射线粉末衍射(XPRD)、N2-吸附脱附比表面仪、透射电镜(TEM)和扫描电镜(SEM)等手段,对其组成、结构和表面形貌进行了表征。
将负载金鸡纳碱伯胺催化剂2a-d应用于苯甲醛及其衍生物与环己酮和环戊酮的不对称Aldol反应,探讨了催化反应的最佳实验条件。在25℃、2 mL水中、7.5mol%2a作催化剂条件下,反应96 h,对硝基苯甲醛与环己酮的Aldol反应能达到95.8%收率、96.4%ee的对映选择性和90/10的dr值。反应结束后,通过过滤实现催化剂的回收和重复使用,但重复四次后,产率、ee值和dr值都明显降低。
Cinchona alkaloids had been researched and attracted people's attention for decades. Due to its rigid frame and active sites, it was widely applied in asymmetric catalytic reactions with excellent catalytic properties. In 1995, Henri Brunner introduced amino-group instead of hydroxyl group in C9 of cinchona alkaloids, and opened the door of research 9-amino cinchona alkaloids derivatives in asymmetric catalytic reactions.
In this thesis, the low-cost and facile cinchonidine as the raw material,9-hydroxyl group was substituted by 9-amino group with simultaneous Walden inversion to give 9-amino cinchona alkaloid 1. Polyacrylonitrile polymer-supported cinchona alkaloid primaryamine cataysts 2a-d were prepared by reaction of the obtained 9-amino cinchona alkaloid 1 with acrylonitrile in different molar ratioes for the first time.
The structures and surface morphologies of polymer catalysts 2a-d had been characterized by NMR, FT-IR, TG, XPRD, N2 adsorption-desorption isothermal curve, TEM and SEM.
The synthesized catalysts 2a-d were applied in the asymmetric Aldol reaction of p-nitroben-zaldehyde with cyclohexanone, and the optimum experimental conditions were screened in details. The product 5a in 95.8% yield,96.4% ee and 90/10 dr was obtained at 25℃for 96 h in 2 mL water and 7.5 mol% catalyst 2a. After the reaction was completed, the catalyst 2a could be recovered by filtration and reused in the asymmetric Aldol reaction. However, yield, ee and dr were reduced sharply after fourth recycled times.
引文
[1]Nicholas, E.; Leadbeater.; and Maro, M. Preparation of Polymer-Supported Ligands and Metal Complexes for Use in Catalysis. Chem.Rev.,2002,]02,3217-3274
[2]Catherine, A. M.; Mark, J. D.; and Mark, B. Recoverable Catalysis and Reagents Using Recyclable Polystyrene-Based Supports. Chem.Rev.,2002,102,3275-3300
[3]Fan, Q. H.; Li Y. M.; and Albert, S. C. C. Recoverable Catalysts for Asymmetric Organic Synthesis. Chem.Rev.2002.102,3385-3466
[4]Song, C. E.; and Lee, S. Supported Chiral Catalysts on Inorganic Materials. Chem.Rev.2002, 102,3495-3524
[5]Kolb,H. C; VanNieuwenhze, M. S, and Sharpless, K. B. Catalytic Asymmetric Dihydroxylation. Chem.Rev.1994,94,2483-2547
[6]Kolb, H. C. and Sharpless, K. B. In Transition Metal for Organic Synthesis,Vol.2(eds M.Beller and C.Bolm), Wiely-VCH Verlag GmbH,Weinheim,1998,219-242
[7]Johnson,R. A. and Sharpless, K. B. In Catalytic Asymmetric synthesis,2nd edn (ed.I.S Ojima), John Wiely&Sons,Inc,New York,2000,357-398
[8]Hoffmann, H. Martin R.; Frackenpohl, Jens. Recent advances in Cinchona alkaloid chemistry. Eur. J. Org. Chem,2004,21,4293-4312.
[9]Henri Brunner; Jurgen Bugler; and Bernhard Nuber. Preparation of 9-Amino(9-deoxy)cinchona Alkaloids Tetrahedron:Asymmetry,1995,6,1699-1702
[10]Henri Brunner and Peter Schmidt Asymmetric Catalysis,131 Naproxen Derivatives by Enantioselective Decarboxylation Eur. J. Org. Chem.2000,2119-2133
[11]Henri Brunner and Markus A. Baur a-Amino Acid Derivatives by Enantioselective Decarboxylation Eur. J. Org. Chem.2003,2854-2862
[12]Louis M.-A. Rogers, Jacques Rouden, Ludovic Lecomte and Marie-Claire Lasne Enantioselective decarboxylation-reprotonation of an a-amino malonate derivative as a route to optically enriched cyclic a-amino acid Tetrahedron Letters,2003,44,3047-3050
[13]Benedek Vakulya, Szilard Varga, Antal Csampai, and Tibor Soos Highly Enantioselective Conjugate Addition of Nitromethane to Chalcones Using Bifunctional Cinchona Organocatalysts Org. Lett.,2005,7,1967-1969
[14]Jian Lv, Jiaming Zhang, Zhu Lin, and Yongmei Wang Enantioselective Synthesis of Functionalized Nitrocyclopropanes by Organocatalytic Conjugate Addition of Bromonitroalkanes to a,b-Unsaturated Enones Chem. Eur. J.2009,15,972-979
[15]Li-ting Dong, Rui-jiong Lu, Quan-sheng Du, Jun-min Zhang, Sheng-ping Liu, Yi-ning Xuan, Ming Yan Highly enantioselective conjugate addition of 1-bromonitroalkanes to a,b-unsaturated ketones catalyzed by 9-amino-9-deoxyepiquinine Tetrahedron,2009,65,4124-4129
[16]Jeremiah P. Malerich, Koji Hagihara, and Viresh H. Rawal Chiral Squaramide Derivatives are Excellent Hydrogen Bond Donor Catalysts J. Am. Chem. Soc.2008,130,14416-14417
[17]JianWu Xie, Wei Chen, Rui Li, Mi Zeng, Wei Du, Lei Yue, Ying-Chun Chen, YongWu, Jin Zhu, and Jin-Gen Deng Highly Asymmetric Michael Addition to a,b-Unsaturated Ketones Catalyzed by 9-Amino-9-deoxyepiquinine Angew. Chem. Int. Ed.2007,46,389-392
[18]Lei Yue, Wei Du, Yan-Kai Liu, Ying-Chun Chen Organocatalytic asymmetric direct Michael addition of aromatic ketones to alkylidenemalononitriles Tetrahedron Letters.,2008,49 3881-3884
[19]Tai-Ran Kang, Jian-Wu Xie, Wei Du, Xin Feng and Ying-Chun Chen Stereoselective desymmetrisation of prochiral a,a-dicyanoalkenes via domino Michael-Michael addition reactions Org. Biomol. Chem.,2008,6,2673-2675
[20]Xiaojie Lu and Li Deng Asymmetric Aza-Michael Reactions of a,b-Unsaturated Ketones with Bifunctional Organic Catalysts Angew. Chem. Int. Ed.2008,47,7710-7713
[21]Guangshun Luo, Shilei Zhang, Wenhu Duan,Wei Wang Enantioselective Conjugate Addition of N-Heterocycles to a,b-Unsaturated Ketones Catalyzed by Chiral Primary Amines Synthesis, 2009,9,1564-1572
[22]Sanjib Gogoi, Cong-Gui Zhao, and Derong Ding Enantioselective Synthesis of β-(3-Hydro-xypyrazol-1-yl) Ketones Using an Organocatalyzed Michael Addition Reaction Org. Lett.,2009,11, 2249-2252
[23]Bin Tan, Pei Juan Chua, Yongxin Li, and Guofu Zhong Organocatalytic Asymmetric Tandem Michael-Henry Reactions:A Highly Stereoselective Synthesis of Multifunctionalized Cyclohexanes with Two Quaternary Stereocenters Org. Lett.,2008,10,2437-2440
[24]Bin Tan, Pei Juan Chua, Xiaofei Zeng, Min Lu, and Guofu Zhong A Highly Diastereo-and Enantioselective Synthesis of Multisubstituted Cyclopentanes with Four Chiral Carbons by the Organocatalytic Domino Michael-Henry Reaction Org. Lett.,2008,10,3489-3492
[25]He Wei, Zhang Bangle, Liu Peng, Sun Xiaoli, Zhang Shengyong Synthesis of Chiral Diamine Ligands Derived from Cinchona Alkaloids and Their Catalytic Performance for Asymmetric Transfer Hydrogenation Chin J Catal,2006,27.527-531
[26]Wei He, Peng Liu, Bang Le Zhang, Xiao Li Sun and Sheng Yong Zhang Efficient iridium and rhodium-catalyzed asymmetric transfer hydrogenation using 9-amino(9-deoxy) cinchona alkaloids as chiral ligands Appl. Organometal. Chem.2006,20,328-334
[27]Wei He, Bang-Le Zhang, Ru Jiang, Peng Liu, Xiao-Li Sun and Sheng-Yong Zhang Novel recoverable catalysts for asymmetric transfer hydrogenation Tetrahedron Letters,2006,47,5367-5370
[28]Heyan Jiang, Chaofen Yang, Chun Li, Haiyan Fu, Hua Chen, Ruixiang Li, and Xianjun Li Heterogeneous Enantioselective Hydrogenation of Aromatic Ketones Catalyzed by Cinchona-and Phosphine-Modified Iridium Catalysts Angew. Chem. Int. Ed.2008,47,9240-9244
[29]Baolei Zheng, Quanzhong Liu, Chuansheng Guo, Xuelian Wang and Long He Highly enantioselective direct aldol reaction catalyzed by cinchona derived primary amines Org. Biomol.Chem,2007,5,2913-2915
[30]Jiarong Chen, Xiaolei An, Xiaoyu Zhu, Xufan Wang, and Wenjing Xiao Rational CombiNat-ion of Two Privileged Chiral Backbones:Highly Efficient Organocatalysts for Asymmetric Direct Aldol Reactions between Aromatic Aldehydes and Acylic Ketones J. Org. Chem.,2008,73, 6006-6009
[31]Jian Zhou, Vijay Wakchaure, Philip Kraft, and Benjamin List Primary-Amine-Catalyzed Enantioselective Intramolecular Aldolizations Angew. Chem. Int. Ed.,2008,47,7656-7658
[32]Wei Chen, Wei Du, Yongzheng Duan, Yong Wu, Shengyong Yang, and Yingchun Chen Enantioselective 1,3-Dipolar Cycloaddition of Cyclic Enones Catalyzed by Multifunctional Primary Amines:Beneficial Effects of Hydrogen Bonding Angew. Chem. Int. Ed.,2007,46,7667-7670
[33]Ravi P. Singh, Keith Bartelson, Yi Wang, Heng Su, Xiaojie Lu, and Li Deng Enantioselective Diels-Alder Reaction of Simple r,a-Unsaturated Ketones with a Cinchona lkaloid Catalyst J. Am. Chem. Soc.,2008,130,2422-2423
[34]Corinna M. Reisinger, Xingwang Wang, and Benjamin List Catalytic Asymmetric Hydroperoxidation of a,b-Unsaturated Ketones:An Approach to Enantiopure Peroxyhemiketals, Epoxides, and Aldols Angew. Chem. Int. Ed.,2008,47,8112-8115
[35]Yongqiang Wang; Jun Song; Ran Hong, Hongming Li; Li Deng Asymmetric Friedel-Crafts Reaction of Indoles with Imines by an Organic Catalyst. J. Am. Chem. Soc.,2006,128,8156-8157
[36]Marcelli, Tommaso; Hiemstra, Henk. Cinchona alkaloids in asymmetric organocatalysis. Synthesis,2010,8,1229-1279
[37]Yu, P., He, J., and Guo, C.9-Thiourea Cinchona alkaloid supported on mesoporous silica as a highly enantioselective, recyclable heterogeneous asymmetric catalyst. Chem.Commum.2008,20, 2355-2357
[38]Youk, S.H., Oh, S.H., Rho, H.S., Lee, J.E.,Lee, J.W., and Song, C.E. Chem.Commum.,2008,2220-2222.
[39]Kim, B. M.; Sharpless, K. B. Heterogeneous catalytic asymmetric dihydroxylation:use of a polymer-bound alkaloid. Tetrahedron Leters.1990,31,3003-3006
[40]Pini, D.; Petri, A.; Salvadori, P. A new crosslinked polymer for the heterogeneous catalytic asymmetric dihydroxylation of alkenes. Tetrahedron: Asymmetry,1993,4,2351-2354
[41]Chinchilla, R.; Mazon, P.; Najera, C. Asymmetric Synthesis of R-Amino Acids Using Polymer-Supported Cinchona Alkaloid-Derived Ammonium Salts as Chiral Phase-Transfer Catalysts. Tetrahedron: Asymmetry,2000,11,3277-3281.
[42]Thierry, B.; Plaquevent, J.-C.; Cahard, D. Poly(ethylene glycol) Supported Cinchona Alkaloids as Phase Transfer Catalysts:Application to the Enantioselective Synthesis of R-Amino Acids. Tetrahedron:Asymmetry,2003,14,1671-1677.
[43]Danelli, T.; Annunziata, R.; Benaglia, M.; Cinquini, M.; Cozzi, F.;Tocco, G. Immobilization of Catalysts Derived from CinchonaAlkaloids on Modified Poly(ethylene glycol). Tetrahedron: Asymmetry.2003,14,461-467
[44]Han, H.; Janda, K. D. A soluble polymer-bound approach to the Sharpless catalytic asymmetric dihydroxylation (AD) reaction:preparation and application of a [(DHQD)2PHAL-PEG-OMe) ligand. Tetrahedron Letters.,1997,38,1527-1530
[45]Han, H.; Janda, K. D. Multipolymer-supported substrate and ligand approach to the Sharpless asymmetric dihydroxylation. Angew. Chem., Int. Ed.,1997,16,1731-1733
[46]Lee, H. M.; Kim, S.; Hyeon, T.; Kim, B. M. Asymmetric dihydroxylation using heterogenized cinchona alkaloid ligands on mesoporous silica. Tetrahedron:Asymmetry.,2001,11,1537-1541
[47]Zhang, Shupeng; Fu, Xiangkai; Fu, Shaodong; Pan, Junfeng. Highly efficient 4-phenoxy substituted organocatalysts derived from N-prolylsulfonamide for the asymmetric direct aldol reaction on water. Catalysis Communications,2009,10,401-405.
[48]Zhang, Shupeng; Fu, Xiangkai; Fu, Shaodong. Rationally designed 4-phenoxy substituted prolinamide phenols organocatalyst for the direct aldol reaction in water. Tetrahedron Letters.2009, 50,1173-1176.
[49]Fu, Shaodong; Fu, Xiangkai; Zhang, Shupeng; Zou, Xiaochuan; Wu, Xiaoju. Highly diastereo and enantioselective direct aldol reactions by 4-tert-butyldimethylsiloxy-substituted organocatalysts derived from N-prolylsulfonamides in water. Tetrahedron:Asymmetry,2009,20,2390-2396
[50]Wu, Chuanlong; Fu, Xiangkai; Ma, Xuebing; Li, Shi. One-step, efficient synthesis of combined threonine-surfactant organocatalysts for the highly enantioselective direct aldol reactions of cyclic ketones with aromatic aldehydes in the presence of water. Tetrahedron:Asymmetry,2010,21,2465-2470.
[51]Wu, Chuanlong; Fu, Xiangkai; Li, Shi. A highly efficient, large-scale, asymmetric direct aldol reaction employing simple threonine derivatives as recoverable organocatalysts in the presence of water. Eur. J. Org. Chem,2011,7,1291-1299,